The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functiona...The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.展开更多
Small-diameter(<6mm)vascular grafts are increasingly needed in peripheral vascular surgery but have few successes because of acute thrombosis,incomplete endothelialization and intimal hyperplasia after implantation...Small-diameter(<6mm)vascular grafts are increasingly needed in peripheral vascular surgery but have few successes because of acute thrombosis,incomplete endothelialization and intimal hyperplasia after implantation.This study used electrospun poly(ε-caprolactone)as the matrix material.Heparin and selenium-containing catalyst-organoselenium modified polyethyleneimine were introduced through layer-by-layer assembly in order to build a vascular graft with in situ nitric oxide(NO)generation.The aim of this study was to explore the application of the graft with improved histocompatibility and biological function for vascular implantation in rats.After implantation in rats,compared to poly(ε-caprolactone),the modified grafts could promote the adhesion and proliferation of endothelial cells,and inhibit the adhesion of smooth muscle cells.The modified grafts remarkably promoted endothelialization,inhibited intimal hyperplasia and increased the ratio of alternatively activated macrophages(M2)to classical activated macrophages(M1).This work constructed a vascular graft with heparinization and catalytic NO generation for improving the vascularization,and accelerating the tissue regeneration by regulating the inflammatory response.The present study indicates that it is a promising method for regulating response and tissue regeneration of small diameter vascular grafts by a novel approach of combining heparinization and catalytic NO generation.展开更多
In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can...In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.展开更多
Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeuti...Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.展开更多
Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually s...Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.展开更多
BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with ...BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.展开更多
Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investi...Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.展开更多
Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea p...Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.展开更多
BACKGROUND Cardiac arrest after noncardiac surgery is a dangerous complication that may contribute to mortality.Because of the high mortality rate and many complications of cardiac arrest,it is very important to ident...BACKGROUND Cardiac arrest after noncardiac surgery is a dangerous complication that may contribute to mortality.Because of the high mortality rate and many complications of cardiac arrest,it is very important to identify and correct a reversible etiology early.By reporting the treatment process of this case,we aimed to broaden the diagnosis and treatment of cardiac arrest after noncardiac surgery and describe how cardiopulmonary resuscitation using extracorporeal membrane oxygenation(ECMO)can improve a patient’s chance of survival.CASE SUMMARY A 69-year-old man visited our hospital complaining of low back pain on July 12,2021.Magnetic resonance imaging showed lumbar disc herniation.Two hours after lumbar disc herniation surgery,the patient developed cardiac arrest.Cardiopulmonary resuscitation was performed,and ECMO was started 60 min after the initiation of cardiopulmonary resuscitation.Regarding the etiology of early cardiac arrest after surgery,acute myocardial infarction and pulmonary embolism were considered first.Based on ultrasound evaluation,acute myocardial infarction appeared more likely.Coronary angiography confirmed occlusion of the left anterior descending branch,and coronary artery stenting was performed.Pulmonary artery angiography was performed to exclude pulmonary embolism.Due to heparinization during ECMO and coronary angiography,there was a large amount of oozing blood in the surgical incision.Therefore,heparinfree ECMO was performed in the early stage,and routine heparinized ECMO was performed after hemorrhage stabilization.Eventually,the patient was discharged and made a full neurologic recovery.CONCLUSION For early postoperative cardiac arrest,acute myocardial infarction should be considered first,and heparin should be used with caution.展开更多
基金Project (31100693/C100302) supported by the National Natural Science Foundation of ChinaProject (31011120049) supported by the Australia-China Special Fund, International Science Linkages Program co-supported by the Department of Innovation, Industry, Science and Research of Australia, and the Ministry of Science and Technology and National Science Foundation of China+1 种基金Project(2010ZDKG-96) supported by the Major Subject of "13115" Programs of Shaan’xi Province, ChinaProject (2012CB619102) supported by the National Basic Research Program of China
文摘The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.
基金National Key Research Program of China(2017YFC1103500)National Natural Science Foundation of China(81671842),PCSIRT(IRT13023)+1 种基金Tianjin Natural Science Foundation(16JCZDJC37600)the State Key Laboratory of Medicinal Chemical Biology(201603007).
文摘Small-diameter(<6mm)vascular grafts are increasingly needed in peripheral vascular surgery but have few successes because of acute thrombosis,incomplete endothelialization and intimal hyperplasia after implantation.This study used electrospun poly(ε-caprolactone)as the matrix material.Heparin and selenium-containing catalyst-organoselenium modified polyethyleneimine were introduced through layer-by-layer assembly in order to build a vascular graft with in situ nitric oxide(NO)generation.The aim of this study was to explore the application of the graft with improved histocompatibility and biological function for vascular implantation in rats.After implantation in rats,compared to poly(ε-caprolactone),the modified grafts could promote the adhesion and proliferation of endothelial cells,and inhibit the adhesion of smooth muscle cells.The modified grafts remarkably promoted endothelialization,inhibited intimal hyperplasia and increased the ratio of alternatively activated macrophages(M2)to classical activated macrophages(M1).This work constructed a vascular graft with heparinization and catalytic NO generation for improving the vascularization,and accelerating the tissue regeneration by regulating the inflammatory response.The present study indicates that it is a promising method for regulating response and tissue regeneration of small diameter vascular grafts by a novel approach of combining heparinization and catalytic NO generation.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)Youth Guidance Project{Qian Kehe Foundation-[2024]Youth 307}。
文摘In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.
基金supported by the Natural Science Foundation of Jiangsu Province(BE2021623,BK20220155)Natural Science Foundation of Jiangsu Province(BE2021623)+4 种基金National Natural Science Foundation of China(32001665,U1903205,32021005)the National Key Research and Development Program of China(2017YF0400303)the Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)the Key Research and Development 303 Program of Ningxia(2020BFG02012)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.
文摘Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.
文摘BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.
文摘Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.
文摘Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.
基金Supported by The Science and Technology Project of Jiaxing,No.2020AD30047 and No.2019AD32231The Key Medical Disciplines of Jiaxing,No.04-Z-08The Key Research Project of Zhejiang Science and Technology Department,No.2020C03019.
文摘BACKGROUND Cardiac arrest after noncardiac surgery is a dangerous complication that may contribute to mortality.Because of the high mortality rate and many complications of cardiac arrest,it is very important to identify and correct a reversible etiology early.By reporting the treatment process of this case,we aimed to broaden the diagnosis and treatment of cardiac arrest after noncardiac surgery and describe how cardiopulmonary resuscitation using extracorporeal membrane oxygenation(ECMO)can improve a patient’s chance of survival.CASE SUMMARY A 69-year-old man visited our hospital complaining of low back pain on July 12,2021.Magnetic resonance imaging showed lumbar disc herniation.Two hours after lumbar disc herniation surgery,the patient developed cardiac arrest.Cardiopulmonary resuscitation was performed,and ECMO was started 60 min after the initiation of cardiopulmonary resuscitation.Regarding the etiology of early cardiac arrest after surgery,acute myocardial infarction and pulmonary embolism were considered first.Based on ultrasound evaluation,acute myocardial infarction appeared more likely.Coronary angiography confirmed occlusion of the left anterior descending branch,and coronary artery stenting was performed.Pulmonary artery angiography was performed to exclude pulmonary embolism.Due to heparinization during ECMO and coronary angiography,there was a large amount of oozing blood in the surgical incision.Therefore,heparinfree ECMO was performed in the early stage,and routine heparinized ECMO was performed after hemorrhage stabilization.Eventually,the patient was discharged and made a full neurologic recovery.CONCLUSION For early postoperative cardiac arrest,acute myocardial infarction should be considered first,and heparin should be used with caution.
